Initial studies confirm that systemic administration of morphine (50 mg/kg) in male Fisher 344N rats resulted in a suppression of NK cell activity. Intracerebroventricular administrations were also found to produce a dose dependent suppression of NK cell activity. In order to localize the CNS effects of morphine on immune function, rats were implanted with bilateral cannulae guides aimed for various brain structures. One week following surgery the animals received bilateral injections of morphine (5 ug in 1 ul saline) in each structure. Three hours following administration of morphine the rats were sacrificed, spleens removed, and both NK measured. Injections of morphine into the anterior hypothalamus arcuate nucleus, medial amygdala, medial thalamus, and dorsal hippocampus had no significant effect on the parameters of immunocompetence examining, when compared to uninjected animals. Injection of morphine into the periaqueductal tray matter, however, produced a suppression of immune function, when compared to saline injected animals. These findings suggest that the central actions of opiates on immune function are mediated through the PAG. The precise neural mechanisms involved, however, remain to be elucidated.